Antibodies against alpha-synuclein: tools and therapies

J Neurochem. 2019 Sep;150(5):612-625. doi: 10.1111/jnc.14713. Epub 2019 Jun 25.

Abstract

Synucleinopathies including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are characterized by the abnormal accumulation and propagation of α-synuclein (α-syn) pathology in the central and peripheral nervous system as Lewy bodies or glial cytoplasmic inclusions. Several antibodies against α-syn have been developed since it was first detected as the major component of Lewy bodies and glial cytoplasmic inclusions. Over the years, researchers have generated specific antibodies that alleviate the accumulation of intracellular aggregated α-syn and associated pathology in cellular and preclinical models of synucleinopathies. So far, antibodies have been the first choice as tools for research and diagnosis and currently, a wide variety of antibody fragments have been developed as an alternative to full-length antibodies for increasing its therapeutic usefulness. Recently, conformation specific antibody-based approaches have been found to be promising as therapeutic strategies, both to block α-syn aggregation and ameliorate the resultant cytotoxicity, and as diagnostic tools. In this review, we summarize different α-syn specific antibodies and provide their usefulness in tackling synucleinopathies. This article is part of the Special Issue "Synuclein".

Keywords: antibodies; synucleinopathies; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies / immunology*
  • Antibodies / therapeutic use
  • Antibodies, Bispecific / immunology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antibody Specificity
  • Biomarkers
  • Delayed Diagnosis
  • Epitopes / immunology
  • Humans
  • Immunoglobulin Fragments / immunology
  • Immunologic Tests / methods
  • Parkinson Disease / diagnosis
  • Parkinson Disease / immunology
  • Parkinson Disease / therapy
  • Protein Aggregation, Pathological / immunology
  • Protein Aggregation, Pathological / prevention & control
  • Protein Conformation
  • Protein Engineering
  • Recombinant Proteins / immunology
  • Single-Domain Antibodies / immunology
  • Synucleinopathies / diagnosis
  • Synucleinopathies / immunology
  • Synucleinopathies / therapy*
  • alpha-Synuclein / antagonists & inhibitors
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / immunology*

Substances

  • Antibodies
  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Biomarkers
  • Epitopes
  • Immunoglobulin Fragments
  • Recombinant Proteins
  • Single-Domain Antibodies
  • alpha-Synuclein